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Updated: Feb 24, 2026
08:02
Live-cell Imaging of Endocytic Transport using Functionalized Nanobodies in Cultured Cells
Published on: October 17, 2025
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Elevated endocytic trafficking mediated by GPRASP2 maintains HSC fidelity
Alanna V Van Huizen1, Mattieu Zhai1, Haruhito Totani2
1Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Biorxiv : the Preprint Server for Biology
|February 23, 2026
Summary
Quiescent hematopoietic stem cells (HSCs) use increased endocytosis, regulated by GPRASP2, to maintain self-renewal and prevent exhaustion. This process limits signaling, ensuring stem cell function.
Area of Science:
- Cell Biology
- Hematopoiesis
- Stem Cell Biology
Background:
- Endolysosomal trafficking is crucial for cellular homeostasis and signaling regulation.
- Hematopoietic stem cell (HSC) maintenance requires balancing quiescence and activation.
- The role of endocytic pathways in HSC quiescence and function is not fully understood.
Purpose of the Study:
- To investigate the role of endocytosis in maintaining quiescent HSC self-renewal.
- To identify specific proteins involved in endocytic regulation of HSC function.
- To elucidate the mechanism by which endocytosis influences HSC signaling and proliferation.
Main Methods:
- Analysis of endocytic activity in quiescent HSCs.
- Investigation of the role of GPRASP2 in HSC endocytosis and function.
- Assessment of HSC proliferation and signaling following disruption of GPRASP2-mediated endocytosis.
Main Results:
- Quiescent HSCs exhibit elevated endocytosis essential for self-renewal.
- GPRASP2 is identified as a key protein mediating endocytosis in HSCs.
- Disruption of GPRASP2-mediated endocytosis leads to increased HSC proliferation and signaling.
Conclusions:
- Elevated endocytosis, mediated by GPRASP2, is critical for maintaining HSC quiescence and self-renewal.
- Endocytosis acts as a mechanism to attenuate signaling by receptor internalization, preventing HSC exhaustion.
- Targeting endocytic pathways may offer strategies to manage HSC function and prevent age-related stem cell dysfunction.
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